The acidic NSAID possesses various pharmacological activities such as anti-inflammatory, analgesic and antipyretic activities. Immediate effect is desired for achieving the analgesic and anti-pyretic activities soon after the oral preparation has been administered Of the preparations administered orally, tablets are most suited in view of compliance by patients, and hence, tablets comprising the acidic NSAID, which is absorbed rapidly, are desired.
Injectable preparations, such as ketoprofen subcutaneous injectable preparation and aspirin D-lysinate intravenous injectable preparation, have been developed so far in order to achieve quicker emergence of effects than do the preparations for oral administration.
However, while injectable preparations may achieve the immediate effects, their application is limited due to the mode of administration. Moreover, they can cause troubles such as constriction of quadriceps femoris muscle liable to such side effects as fibrosis of muscle tissues.
Under these circumstances, preparations for oral administration, containing an acidic NSAID, that may be absorbed quickly and that have decreased side effects are wanted.
In general, the acidic NSAID is sparlingly soluble in water at a pH range of from acidic to weak acidic, if they are in the crystalline state. Therefore, absorption of the acidic NSAID tends to be delayed or decreased at the upper small intestine, when they are administered in the crystalline state.
Meanwhile, the acidic NSAID tends to cause gastric disorders, when they are administered orally in a dissolved state, as they are absorbed from the stomach in the non-ionic form by the influence of pH in the stomach.
From the above standpoints of view, it is considered to be a problem to be solved to prepare acidic NSAID preparations that pass the stomach in the crystalline state and that dissolve quickly at a region from the outlet of the stomach to the inlet of the small intestine, in order to develop acidic NSAID preparations having the immediate analgesic and anti-pyretic effects and having the decreased side effects.
Thus, we aimed at the relationship between the solubility of the acidic NSAID and the pH of the site at which they are absorbed. Namely, we tried to improve the solubility of the acidic NSAID in the crystalline state at a pH region of 5.8-6.5 and to elucidate substances that can mask the acid moiety of the acidic NSAID. This was in pursuit of substances whereby oral preparations may be obtained to achieve a high absorption rate, a high bioavailability (AUC or the integral of blood concentration curve) and a reduced irritation upon administration.
As a result, we have found that certain protein hydrolyzates such as hydrolyzate of gelatin or casein, or polypeptides possess the above-mentioned properties, leading to the completion of the present invention.